This invention relates to salt forms and polymorphs of N,2-dimethyl-6-[7-(2-morpholinoethoxy)quinolin-4-yloxy]benzofuran-3-carboxamide that are useful in the treatment of abnormal cell growth, such as cancer, in mammals. This invention also relates to compositions including such salts and polymorphs, and to methods of using such compositions in the treatment of abnormal cell growth in mammals, especially humans.
The compound N,2-dimethyl-6-[7-(2-morpholinoethoxy)quinolin-4-yloxy]benzofuran-3-carboxamide, shown in structural formula 1 in its free base form,
is a potent, selective inhibitor of vascular endothelial growth factor receptor 2 (VEGF-R2). It potently inhibits the tyrosine kinase activity of VEGF-R2 and selectively blocks VEGF-stimulated receptor autophosphorylation, as well as endothelial cell survival. In vivo studies have shown that this compound produced significant inhibition of vascular permeability, tumor angiogenesis, and the growth of human xenograft tumors. This compound has been described in the published U.S. patent application US 2005-0137395, published Jun. 23, 2005, the disclosure of which is incorporated herein by reference in its entirety. Methods of making the free base form of compound 1 are also described in the U.S. provisional application 60/742,847, entitled “METHODS OF PREPARING A VEGF-R INHIBITOR”, filed on Dec. 5, 2005.
It is advantageous to have salt and polymorphic forms having improved properties, such as improved crystallinity, dissolution properties, and/or decreased hygroscopicity, while maintaining chemical and enantiomeric stability properties.